Models of addiction have been essential for uncovering the neurobiological factors associated with drug-seeking behavior. In addition to the use of typical mammalian models, development of simplified systems for the study of addiction may contribute significant new experimental opportunities for an analysis of widely conserved underlying neural processes. The increased inclusion of invertebrate models for the study of fundamental phenomena is also consistent with current goals and guidelines in the ethics of animal use. In recent work, we have demonstrated that drugs of abuse are associated with rewarding properties for place-conditioning in crayfish. The experimental advantages of crayfish include a relatively simple and accessible CNS organization, and sets of conspicuous, stereotyped behavior patterns amenable to effective quantitative analysis. This grant aims to develop initial findings into a robust model for the study of drug-reward with a characterization (1) of drug-induced changes in locomotion and amine hemolymph release, (2) of sensitization and dose-response relationships in a place conditioning paradigm, and (3) of an automated, operant self-administration paradigm. Successful completion will allow us to advance a novel experimental system of drug-reward. With multiple levels of organization readily accessible, a detailed characterization of this intriguing behavioral phenomenon in a species not particularly known for its cognitive abilities will provide a unique, comparative ethological perspective on the neural substrates responsive to drugs of abuse, the nature of reward mechanisms, drug-seeking, and motivated behaviors in general. In sum, the continued development of novel experimental paradigms, such as those described here, promise to provide new insights into the evolutionarily derived neurochemical systems from which human drug addictions stem.